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Biomedical subjects

H S Asgari

Publications and source records attributed to H S Asgari.

9 recordsLinked to original sources

Echo-planar perfusion-sensitive MR imaging of acute cerebral ischemia.

T2*-sensitive echo-planar magnetic resonance imaging was used with first-pass magnetic susceptibility contrast enhancement in a cat model of acute regional stroke to evaluate the relationship between cerebral hypoperfusion and ischemic brain damage. In normal brain, dose-dependent decreases in signal intensity were observed after intravenous injection of 0.15-0.50 mmol/kg dysprosium-diethylenetriaminepentaacetic acid bismethylamide or gadodiamide injection. Shortly after unilateral occlusion of the middle cerebral artery, foci of signal hyperintensity on diffusion-weighted images were observed in the ipsilateral basal ganglia. Sixty minutes after occlusion, perfusion deficits in the ipsilateral parietal and temporal cortical gray matter were observed to be spatially correlated with areas of hyperintensity on diffusion-weighted images. When reflow was attempted after 60 minutes, delayed contrast agent transit suggestive of partial ischemic tissue injury was demonstrated. Attempts to produce reflow after 2 hours did not restore normal brain perfusion and resulted in image hyperintensity and histopathologic brain damage. Six-hour occlusion was associated with pronounced perfusion deficits in the ischemic territory.

Acute Disease↗

Diffusion/perfusion MR imaging of acute cerebral ischemia.

In vivo echo-planar MR imaging was used to measure apparent diffusion coefficients (ADC) of cerebral tissues in a comprehensive noninvasive evaluation of early ischemic brain damage induced by occlusion of the middle cerebral artery (MCA) in a cat model of acute regional stroke. Within 10 min after arterial occlusion, ADC was significantly lower in tissues within the vascular territory of the occluded MCA than in normally perfused tissues in the contralateral hemisphere. Sequential echo-planar imaging was then used in conjunction with bolus injections of the magnetic susceptibility contrast agent, dysprosium DTPA-BMA, to characterize the underlying cerebrovascular perfusion deficits. Normally perfused regions of brain were identified by a dose-dependent 35-70% loss of signal intensity within 6-8 s of contrast administration, whereas ischemic regions appeared relatively hyperintense. These data indicate that sequential diffusion/perfusion imaging may be useful in differentiating permanently damaged from reversibly ischemic brain tissue.

Animals↗

Anisotropy in diffusion-weighted MRI.

Diffusional anisotropy of water protons, induced by nonrandom, directional barriers which hinder or retard water motion, is measurable by MRI. Faster water diffusion was observed when the diffusion-sensitizing gradient direction paralleled the long axes of white matter tracts, indicative of fewer barriers to water motion. Diffusion perpendicular to this axis was as much as four times slower. Anisotropy was seen pre- and postmortem in all axial, sagittal, and coronal planes, with and without cardiac gating. Ordering has also been observed in feline optic nerve and in human peripheral nerves. Utilization of this technique can greatly improve understanding and assessment of demyelinating disorders, of white matter infarcts and neoplasms, and of neonatal brain and spinal cord development.

Animals↗

Gossypol effects on endothelial cells and tumor blood flow.

Isomers (-, +) of the antitumor agent gossypol (G) were studied for their ability to reduce tumor ATP and blood flow in rats bearing subcutaneously implanted pancreatic tumors. A 50% reduction in tumor ATP/Pi within ih of a single injection of -G was associated with a 60% decline in tumor blood flow. To determine if these changes in tumor physiology could be due to a direct drug effect on tumor endothelium, G isomers were compared for their ability to alter protein (125I-BSA) permeability and metabolic (32P) labelling of cultured endothelial cells. Treatments for ih produced no endothelial cell leakage, but 24h exposures to either -G (5 microM) or +G (50 microM) produced complete permeability of the monolayers to 125I-BSA. In contrast, 0.5-I.Oh exposures to -G (4 microM) produced 2 to 3-fold increases in phosphorylated 27 kDa heat-shock protein, hsp-27. Hsp-27 phosphoprotein isoforms were differentially labelled following -G and +G exposures with the phosphorylation profile of -G appearing most similar to that of oxyradical producing agents known to induce hsp-27 and injure endothelial cells. We postulate that the tumor ischemic effects of -G are mediated by endothelial response to oxyradical production in a mechanism similar to that of tissue ischemia-reperfusion injury.

Adenosine Triphosphate↗

Ischemic brain damage: reduction by sodium-calcium ion channel modulator RS-87476.

A novel sodium-calcium ion channel modulator, RS-87476, reduced cerebral infarct size in cats subjected to permanent unilateral occlusion of the middle cerebral artery. Cerebral injury was assessed in vivo with a combination of magnetic resonance (MR) imaging and spectroscopy for 5-12 hours after occlusion and was compared with the area of histochemically ischemic brain tissue. Compared with infarcts in placebo-treated animals, infarcts in cats given RS-87476 were reduced by an average of 70% at the lowest dose, 75% at the intermediate dose, and 88% at the highest dose. Tissue edema, observed as areas of signal hyperintensity on diffusion- and T2-weighted spin-echo images, was confined to small regions of the parietal cortex and basal ganglia in drug-treated animals. Mean plasma levels of RS-87476 at the lowest dose were 13 ng/mL initially, falling to maintenance levels of 3-5 ng/mL; at the intermediate and highest doses, plasma levels of drug were approximately five- and 20-fold greater. The drug was only slightly hypotensive. At least part of the potent cerebroprotective effects of RS-87476 result from its ability to stabilize metabolic energy reserves, reduce lactate formation in ischemic tissues, and attenuate intracerebral edema.

Animals↗

Ultrafast magnetic resonance imaging: diffusion and perfusion.

Echo-planar magnetic resonance imaging (MRI) can be used to measure apparent diffusion coefficients noninvasively in vivo, with scan times of 150 milliseconds or less, and to assess early ischemic effects in the feline experimental model, which has an occluded middle cerebral artery (MCA). The apparent diffusion coefficient in ischemic regions, which are identified later from vital staining, is significantly decreased from normal values within 1 hour after the MCA becomes occluded. A series of 10 echo-planar images that are progressively diffusion-weighted can be collected in 1 minute (effective TR of 6 seconds). Semilogarithmic plots of image intensity versus gradient strength factors (b values) were linear. Collecting sequential gradient echo-planar images during the passage of a bolus of contrast medium is also useful when assessing perfusion or vascular integrity before and during ischemic episodes. After intravenous injection of dysprosium-diethylene triamine penta-acetic acid-bis(methylamide), typical signal losses of 40% to 80% were observed and were dose-dependent. Areas of possible ischemia identified from diffusion-weighted images did not lose signal intensity with the use of contrast medium and were seen as regions of relative hyperintensity, clearly discernible from normally perfused tissues.

Animals↗

Early detection of ischemic injury: comparison of spectroscopy, diffusion-, T2-, and magnetic susceptibility-weighted MRI in cats.

Within one hour following MCA-occlusion in cats, heavily diffusion-weighted spin-echo MR images exhibited a well-defined hyperintensity in the gray matter and basal ganglia of the occluded side over normal side. This hyperintensity correlated with lactate and inorganic phosphate increases in peak areas from MR surface coil spectroscopy. T2-weighted MRI showed no significant abnormality in signal intensity from the occluded hemisphere within several hours post-occlusion. Using a paramagnetic MR contrast agent, dysprosium-DTPA-BMA together with heavily T2-weighted spin-echo or with T2*-weighted echo-planar (EPI) MR imaging, perfusion deficits resulting from MCA-occlusion were detected as a relative hyperintensity of ischaemic tissues compared to normally-perfused cerebral tissues in the contralateral hemisphere. Evidence of these deficits was observed within minutes of occlusion, and spatially correlated well with the hyperintensity seen on the diffusion-weighted images. Diffusion- and susceptibility-weighted MRI was superior to conventional T2-weighted MRI in the detection of early ischaemic events. In contrast to surface coil spectroscopy, both techniques mapped regions of jeopardy throughout the brain, which later showed T2-weighted hyperintensity and lack of vital (TTC) staining.

Animals↗

Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system.

The diffusion behavior of intracranial water in the cat brain and spine was examined with the use of diffusion-weighted magnetic resonance (MR) imaging, in which the direction of the diffusion-sensitizing gradient was varied between the x, y, and z axes of the magnet. At very high diffusion-sensitizing gradient strengths, no clear evidence of anisotropic water diffusion was found in either cortical or subcortical (basal ganglia) gray matter. Signal intensities clearly dependent on orientation were observed in the cortical and deep white matter of the brain and in the white matter of the spinal cord. Greater signal attenuation (faster diffusion) was observed when the relative orientation of white matter tracts to the diffusion-sensitizing gradient was parallel as compared to that obtained with a perpendicular alignment. These effects were seen on both premortem and immediate postmortem images obtained in all axial, sagittal, and coronal views. Potential applications of this MR imaging technique included the stereospecific evaluation of white matter in the brain and spinal cord and in the characterization of demyelinating and dysmyelinating diseases.

Animals↗